CN103553908B - Preparation method of o-ethoxybenzoic acid - Google Patents
Preparation method of o-ethoxybenzoic acid Download PDFInfo
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- CN103553908B CN103553908B CN201310548024.6A CN201310548024A CN103553908B CN 103553908 B CN103553908 B CN 103553908B CN 201310548024 A CN201310548024 A CN 201310548024A CN 103553908 B CN103553908 B CN 103553908B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
- C07C51/412—Preparation of salts of carboxylic acids by conversion of the acids, their salts, esters or anhydrides with the same carboxylic acid part
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/02—Preparation of carboxylic acids or their salts, halides or anhydrides from salts of carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/10—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with ester groups or with a carbon-halogen bond
- C07C67/11—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with ester groups or with a carbon-halogen bond being mineral ester groups
Abstract
The invention relates to a preparation method of o-ethoxybenzoic acid, which comprises the following steps: adding salicylic acid, acetone and potassium hydroxide into a reaction bulb, dropwisely adding bromoethane while stirring at room temperature, heating under reflux for 9-15 hours, recovering the acetone under reduced pressure, adding water and liquid alkali, heating under reflux for 2-4 hours, cooling to room temperature, regulating the pH value to 3-4 with glacial acetic acid, cooling to 1-15 DEG C, separating by vacuum filtration, washing with water, and carrying out vacuum drying to obtain the o-ethoxybenzoic acid, wherein the salicylic acid:potassium hydroxide:bromoethane:liquid alkali mol ratio is 1:(2.0-2.5):(2.1-2.5):1.4. The method has the advantages of simple technique, low raw material cost, high yield and good quality, and is convenient to operate and convenient for industrial production.
Description
Technical field
The present invention relates to medicine intermediate technical field, specifically, is a kind of preparation method of o-ethoxybenzoic acid.
Background technology
O-ethoxybenzoic acid is a kind of important intermediate of synthesis treatment ED medicine (viagra), it is more that this intermediate synthesizes domestic and international relevant report, typically have following two kinds, one uses 0-chloro-benzoic acid etherificate, and the method raw materials cost is high, and need High Temperature High Pressure operation easier large, be unfavorable for suitability for industrialized production, first by after Whitfield's ointment esterification, through etherificate, alkaline hydrolysis must this product more again for another kind of method, and the method synthesis cost is high, reaction conditions is wayward, is difficult to realize large-scale industrial production.
Summary of the invention
The object of the invention is for deficiency of the prior art, provide a kind of technique simple, easy to operate, material cost is low, is convenient to the o-ethoxybenzoic acid preparation method of suitability for industrialized production.
For achieving the above object, the technical scheme that the present invention takes is: a kind of preparation method of o-ethoxybenzoic acid, by Whitfield's ointment, acetone, potassium hydroxide adds reaction flask, stirring at room temperature drips monobromethane, temperature rising reflux 9 ~ 15 hours, reclaim under reduced pressure acetone, add water and liquid caustic soda, temperature rising reflux 2 ~ 4 hours again, be cooled to room temperature, PH=3 ~ 4 are adjusted with ice acid acid, be cooled to 1 DEG C-15 DEG C again, suction filtration is separated, washing, vacuum-drying obtains o-ethoxybenzoic acid, wherein Whitfield's ointment: potassium hydroxide: monobromethane: these four kinds of material mol ratios of liquid caustic soda are 1:2.0 ~ 2.5:2.1 ~ 2.5:1.4.
Described Whitfield's ointment: potassium hydroxide: monobromethane: these four kinds of material mol ratios of liquid caustic soda are 1:2:2.1:1.4.
Described method is: by Whitfield's ointment 0.36mol, acetone 500ml adds reaction flask, then potassium hydroxide 0.76mol is added, add intensification and be incubated 3 hours at reflux, be cooled to 20 DEG C, add 0.79mol monobromethane, monobromethane dropwises, be warming up to backflow, reflux state is kept to be incubated 10 hours, insulation terminates reclaim under reduced pressure acetone, recover acetone terminates, add 300ml water, 50 gram of 30% liquid caustic soda 0.38mol is warming up to 90 DEG C, and be incubated 2 hours at this temperature, insulation end is cooled to 30 ~ 35 DEG C, add Glacial acetic acid at this temperature, control reaction solution and drop to PH=3 ~ 4, solid is now had to separate out, be further cooled to 14 DEG C, suction filtration, water washing final vacuum is dry, obtain o-ethoxybenzoic acid.
Reaction equation of the present invention is as follows:
The invention has the advantages that: the present invention adopts Whitfield's ointment to be raw material, acetone as solvent, acid binding agent made by potassium hydroxide, monobromethane is made ethylating agent and is first generated o-ethoxybenzoic acid ethyl ester, then steam and desolventize, then add appropriate aqueous sodium hydroxide solution intensification hydrolysis, obtain o-ethoxybenzoic acid salt brine solution, be acidified to PH=3 ~ 4 with Glacial acetic acid, after separation, obtain o-ethoxybenzoic acid.The method technique is simple, and easy to operate, material cost is low, and yield is high, and quality is good, is convenient to suitability for industrialized production.
Embodiment
Below embodiment provided by the invention is elaborated.
Embodiment 1
By Whitfield's ointment 50g (0.36mol), acetone 500ml adds reaction flask, temperature control is less than the potassium hydroxide solid (90%) 42.6 gram (0.76mol) that 40 DEG C add porphyrize, add intensification and be incubated 3 hours at reflux, be cooled to 20 DEG C, slowly drip 86g(0.79mol) monobromethane, monobromethane dropwises, be warming up to backflow, reflux state is kept to be incubated 10 hours, insulation terminates reclaim under reduced pressure acetone, recover acetone terminates, add 300ml water, 50 gram of 30% liquid caustic soda (i.e. the sodium hydroxide of liquid state) (0.38mol) is warming up to 90 DEG C, and be incubated 2 hours at this temperature, insulation end is cooled to 30 ~ 35 DEG C, slowly drip Glacial acetic acid at this temperature, control reaction solution and drop to PH=3 ~ 4, a large amount of solid is now had to separate out, be further cooled to 14 DEG C, suction filtration, water washing final vacuum is dry, obtain o-ethoxybenzoic acid 53.3g(0.32mol), yield 89.10%, purity 99.33%(GC, Conditions Instrument: GC-9790 gas-chromatography, fid detector, chromatographic column model: DM-5,30m 0.25mmID 0.25um, GC testing conditions: detector: FID carrier gas: nitrogen, carrier gas flux: 0.10Mpa, column temperature: 230 DEG C, injector temperature: 260 DEG C, detected temperatures: 270 DEG C, sample concentration 1.0g/10ml acetone solution, sample size: 2ul).
Embodiment 2
By Whitfield's ointment 65g (0.47mol), acetone 400ml adds reaction flask, temperature control is less than the potassium hydroxide solid (90%) 67.3 gram (1.08mol) that 40 DEG C add porphyrize, add intensification and be incubated 3 hours at reflux, be cooled to 20 DEG C, slowly drip 117.8g(1.08mol) monobromethane, monobromethane dropwises, be warming up to backflow, reflux state is kept to be incubated 12 hours, insulation terminates reclaim under reduced pressure acetone, recover acetone terminates, add 500ml water, 62.7 gram of 30% liquid caustic soda (i.e. the sodium hydroxide of liquid state) (0.47mol) is warming up to 90 DEG C, and be incubated 3 hours at this temperature, insulation end is cooled to 30 ~ 35 DEG C, slowly drip Glacial acetic acid at this temperature, control reaction solution and drop to PH=3 ~ 4, a large amount of solid is now had to separate out, be further cooled to 10 DEG C, suction filtration, water washing final vacuum is dry, obtain o-ethoxybenzoic acid 71.3g(0.43), yield 91.24%, purity 99.41%(GC, Conditions Instrument: GC-9790 gas-chromatography, fid detector, chromatographic column model: DM-5,30m 0.25mmID 0.25um, GC testing conditions: detector: FID carrier gas: nitrogen, carrier gas flux: 0.10Mpa, column temperature: 230 DEG C, injector temperature: 260 DEG C, detected temperatures: 270 DEG C, sample concentration 1.0g/10ml acetone solution, sample size: 2ul).
Embodiment 3
By Whitfield's ointment 100g (0.72mol), acetone 900ml adds reaction flask, temperature control is less than the potassium hydroxide solid (90%) 112.2 gram (1.80mol) that 40 DEG C add porphyrize, add intensification and be incubated 3 hours at reflux, be cooled to 20 DEG C, slowly drip 196g(1.80mol) monobromethane, monobromethane dropwises, be warming up to backflow, reflux state is kept to be incubated 15 hours, insulation terminates reclaim under reduced pressure acetone, recover acetone terminates, add 600ml water, 96 gram of 30% liquid caustic soda (i.e. the sodium hydroxide of liquid state) (0.72mol) is warming up to 90 DEG C, and be incubated 4 hours at this temperature, insulation end is cooled to 30 ~ 35 DEG C, slowly drip Glacial acetic acid at this temperature, control reaction solution and drop to PH=3 ~ 4, a large amount of solid is now had to separate out, be further cooled to 1 DEG C, suction filtration, water washing final vacuum is dry, obtain o-ethoxybenzoic acid 103.3g (0.62mol), yield 86.32%, purity 99.51%(GC normalization method, Conditions Instrument: GC-9790 gas-chromatography, fid detector, chromatographic column model: DM-5,30m 0.25mmID 0.25um, GC testing conditions: detector: FID carrier gas: nitrogen, carrier gas flux: 0.10Mpa, column temperature: 230 DEG C, injector temperature: 260 DEG C, detected temperatures: 270 DEG C, sample concentration 1.0g/10ml acetone solution, sample size: 2ul).
Embodiment 4
By Whitfield's ointment 65g (0.47mol), acetone 500ml adds reaction flask, temperature control is less than the potassium hydroxide solid (90%) 52.7 gram (0.94mol) that 40 DEG C add porphyrize, add intensification and be incubated 3 hours at reflux, be cooled to 20 DEG C, slowly drip 107g(0.99mol) monobromethane, monobromethane dropwises, be warming up to backflow, reflux state is kept to be incubated 10 hours, insulation terminates reclaim under reduced pressure acetone, recover acetone terminates, add 300ml water, 62.7 gram of 30% liquid caustic soda (i.e. the sodium hydroxide of liquid state) (0.47mol) is warming up to 90 DEG C, and be incubated 2 hours at this temperature, insulation end is cooled to 30 ~ 35 DEG C, slowly drip Glacial acetic acid at this temperature, control reaction solution and drop to PH=3 ~ 4, a large amount of solid is now had to separate out, be further cooled to 14 DEG C, suction filtration, water washing final vacuum is dry, obtain o-ethoxybenzoic acid 53.3g(0.32mol), yield 89.10%, purity 99.33%(GC, Conditions Instrument: GC-9790 gas-chromatography, fid detector, chromatographic column model: DM-5,30m 0.25mmID 0.25um, GC testing conditions: detector: FID carrier gas: nitrogen, carrier gas flux: 0.10Mpa, column temperature: 230 DEG C, injector temperature: 260 DEG C, detected temperatures: 270 DEG C, sample concentration 1.0g/10ml acetone solution, sample size: 2ul).
Embodiment 5
By Whitfield's ointment 50g (0.36mol), acetone 400ml adds reaction flask, temperature control is less than the potassium hydroxide solid (90%) 50.5 gram (0.9mol) that 40 DEG C add porphyrize, add intensification and be incubated 3 hours at reflux, be cooled to 20 DEG C, slowly drip 98g(0.9mol) monobromethane, monobromethane dropwises, be warming up to backflow, reflux state is kept to be incubated 12 hours, insulation terminates reclaim under reduced pressure acetone, recover acetone terminates, add 500ml water, 71.8 gram of 30% liquid caustic soda (i.e. the sodium hydroxide of liquid state) (0.54mol) is warming up to 90 DEG C, and be incubated 3 hours at this temperature, insulation end is cooled to 30 ~ 35 DEG C, slowly drip Glacial acetic acid at this temperature, control reaction solution and drop to PH=3 ~ 4, a large amount of solid is now had to separate out, be further cooled to 10 DEG C, suction filtration, water washing final vacuum is dry, obtain o-ethoxybenzoic acid 71.3g(0.43), yield 91.24%, purity 99.41%(GC, Conditions Instrument: GC-9790 gas-chromatography, fid detector, chromatographic column model: DM-5,30m 0.25mmID 0.25um, GC testing conditions: detector: FID carrier gas: nitrogen, carrier gas flux: 0.10Mpa, column temperature: 230 DEG C, injector temperature: 260 DEG C, detected temperatures: 270 DEG C, sample concentration 1.0g/10ml acetone solution, sample size: 2ul).
Embodiment 6
By Whitfield's ointment 100g (0.72mol), acetone 900ml adds reaction flask, temperature control is less than the potassium hydroxide solid (90%) 95.4 gram (1.70mol) that 40 DEG C add porphyrize, add intensification and be incubated 3 hours at reflux, be cooled to 20 DEG C, slowly drip 185.1g(1.70mol) monobromethane, monobromethane dropwises, be warming up to backflow, reflux state is kept to be incubated 15 hours, insulation terminates reclaim under reduced pressure acetone, recover acetone terminates, add 600ml water, 141.5 gram of 30% liquid caustic soda (i.e. the sodium hydroxide of liquid state) (0.94mol) is warming up to 90 DEG C, and be incubated 4 hours at this temperature, insulation end is cooled to 30 ~ 35 DEG C, slowly drip Glacial acetic acid at this temperature, control reaction solution and drop to PH=3 ~ 4, a large amount of solid is now had to separate out, be further cooled to 1 DEG C, suction filtration, water washing final vacuum is dry, obtain o-ethoxybenzoic acid 103.3g (0.62mol), yield 86.32%, purity 99.51%(GC normalization method, Conditions Instrument: GC-9790 gas-chromatography, fid detector, chromatographic column model: DM-5,30m 0.25mmID 0.25um, GC testing conditions: detector: FID carrier gas: nitrogen, carrier gas flux: 0.10Mpa, column temperature: 230 DEG C, injector temperature: 260 DEG C, detected temperatures: 270 DEG C, sample concentration 1.0g/10ml acetone solution, sample size: 2ul).
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the prerequisite not departing from the inventive method; can also make some improvement and supplement, these improve and supplement and also should be considered as protection scope of the present invention.
Claims (1)
1. the preparation method of an o-ethoxybenzoic acid, it is characterized in that, by Whitfield's ointment 0.36mol, acetone 500ml adds reaction flask, then potassium hydroxide 0.76mol is added, add intensification and be incubated 3 hours at reflux, be cooled to 20 DEG C, add 0.79mol monobromethane, monobromethane dropwises, be warming up to backflow, reflux state is kept to be incubated 10 hours, insulation terminates reclaim under reduced pressure acetone, recover acetone terminates, add 300ml water, 50 gram of 30% liquid caustic soda 0.38mol is warming up to 90 DEG C, and be incubated 2 hours at this temperature, insulation end is cooled to 30 ~ 35 DEG C, add Glacial acetic acid at this temperature, control reaction solution and drop to PH=3 ~ 4, solid is now had to separate out, be further cooled to 14 DEG C, suction filtration, water washing final vacuum is dry, obtain o-ethoxybenzoic acid.
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| CN103553896B (en) * | 2013-11-11 | 2015-04-29 | 苏州诚和医药化学有限公司 | Method for synthesizing o-ethylsalicylic acid |
| CN105503593A (en) * | 2015-12-30 | 2016-04-20 | 苏州诚和医药化学有限公司 | Synthetic method of methyl o-anisate |
| CN105585482A (en) * | 2015-12-30 | 2016-05-18 | 苏州诚和医药化学有限公司 | Method for one-step synthesis of methyl o-anisate |
| CN105461554A (en) * | 2015-12-30 | 2016-04-06 | 苏州诚和医药化学有限公司 | Preparation method of methyl o-methoxybenzoate |
| CN105622409A (en) * | 2015-12-30 | 2016-06-01 | 苏州诚和医药化学有限公司 | Method for synthesizing methyl o-anisate through methyl bromide |
| CN105566107A (en) * | 2015-12-30 | 2016-05-11 | 苏州诚和医药化学有限公司 | Synthesis method of methyl o-anisate |
| CN105418429B (en) * | 2015-12-30 | 2018-01-05 | 苏州诚和医药化学有限公司 | A kind of method for preparing methyl o-anisate |
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